Baseline Plasma NT-proBNP and Clinical Characteristics: Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction Trial

BackgroundN-terminal B type natriuretic peptide (NT-proBNP) is usually elevated in heart failure (HF) patients with reduced ejection fraction (EF). Less is known about NT-proBNP in HF with preserved EF (HF-PEF). We measured baseline NT-proBNP in 3562 HF-PEF enrolled patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial.Methods and ResultsPatients with EF ≥45%, age ≥60 years, and either New York Heart Association (NYHA) II-IV symptoms with HF hospitalization (HFH) within 6 months or NYHA III-IV symptoms with corroborative evidence of HF or structural changes associated with HF-PEF. NT-proBNP (pg/mL) measured centrally using the Elecsys proBNP assay (Roche). Mean age 72 ± 7 years, 60% were women, the investigator indicated HF etiology was hypertension in 64%; the majority were in NYHA III. Medications included diuretics in 82%, angiotensin-converting enzyme inhibitor in 26%, β-blocker in 59%, and spironolactone in 15%. Median NT-proBNP was 341 pg/mL (interquartile range 135 to 974 pg/mL) and geometric mean was 354 pg/mL. In multivariate analysis, the baseline characteristics most strongly associated with higher NT-proBNP levels were atrial fibrillation (ratio of geometric mean 2.59, P < .001), NYHA IV symptoms (1.52, P < .001), lower estimated glomerular filtration rate (1.44, P < .001), and HFH hospitalization within 6 months (1.37, P < .001).ConclusionsMost HF-PEF patients have elevated NT-proBNP levels. The NT-proBNP concentrations were related to baseline characteristics generally associated with worse outcomes for HF patients.     

Soluble ST2 as a Biomarker for Detecting Stable Heart Failure With a Normal Ejection Fraction in Hypertensive Patients

BackgroundWe investigated the measurement of soluble ST2 (sST2) in stable heart failure (HF) with a normal ejection fraction (HFNEF) in hypertensive patients.Methods and ResultsEchocardiography and serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) and sST2 concentrations were evaluated in 107 hypertensive patients (65 ± 12 years, 57 male) with ejection fraction (EF) >50%. Among them, 68 patients with stable HF in functional class II and III were the HFNEF group. We found that the area under the receiver operating characteristic curve (AUC) for sST2 was 0.80 (95% CI 0.70–0.89; P < .001), relatively better than that for NT-proBNP (AUC 0.70, 95% CI 0.58–0.79; P = .003) to detect HFNEF. However, the NT-proBNP concentration, rather than sST2, was higher in HFNEF patients with functional class III (562 ± 891 vs 185 ± 242 pg/mL in functional class II; P = .009), and correlated better with mitral E/e′ (annular early diastolic velocity) (r = 0.327; P = .008) than sST2 concentrations in HFNEF patients. Multivariate analysis showed that sST2 >13.5 ng/mL was independently associated with HFNEF in hypertensive patients (odds ratio 11.7, 95% CI = 2.9–47.4; P = .001).ConclusionssST2 measurement provides diagnostic aid of stable HFNEF for hypertensive patients. Addition of NT-proBNP to sST2 could give further information regarding HF functional class and diastolic abnormality.     

Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy

BackgroundAmino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for the diagnosis and exclusion of congestive heart failure (HF). Little is known about the effect of race on NT-proBNP concentrations. Also, NT-proBNP levels may be higher in apparently well women, but the effect of gender on NT-proBNP concentrations in dyspneic patients is not known.Methods and ResultsNT-proBNP (Elecsys proBNP, Roche, Indianapolis, IN) was measured in 599 dyspneic patients in a prospective study. Of these, 44 were African American; 295 were female. NT-proBNP levels were examined according to race and gender in patients with and without acute HF using analysis of covariance. Receiver operating characteristic (ROC) curves assessed NT-proBNP by race and gender. Cutpoints for diagnosis (450, 900, and 1800 pg/mL for ages <50, 50 to 75, and >75 years) and exclusion (300 pg/mL) were examined in African-American and female subjects. There was no difference in the rates of acute HF between African-American and non–African-American (30% versus 35%, P = .44) or male and female (35% versus 35%, P = .86) subjects. In subjects with HF, there was no difference in median NT-proBNP concentrations between African American and non–African American (6196 versus 3597 pg/mL, P = .37). In subjects without HF, unadjusted NT-proBNP levels were lower in African-American subjects than in non–African-American subjects (68 versus 148 pg/mL, P < .03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = .53) or without HF (116 pg/mL versus 150 pg/mL, P = .62). Among African Americans, NT-proBNP had an area under the ROC for acute HF of 0.96 (P < .0001), and at optimal cutpoints, had a sensitivity of 100% and a specificity of 90%. Among females, NT-proBNP had an area under the ROC for acute HF of 0.95 (P < .0001), and had a sensitivity of 89% and a specificity of 88%; 300 pg/mL had negative predictive value of 100% in African Americans and females.ConclusionNT-proBNP is useful for the diagnosis and exclusion of acute HF in dyspneic subjects, irrespective of race or gender.     

A Combined-Biomarker Approach to Clinical Phenotyping Renal Dysfunction in Heart Failure

BackgroundDifferentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF.Methods and ResultsA total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/mL) and BUN/creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6–1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2–2.7, P = .008, P interaction = .005).ConclusionsIn the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis.     

CRP,IL-6 and endothelin-1 levels in patients undergoing coronary artery bypass grafting. Do preoperative inflammatory parameters predict early graft occlusion and late cardiovascular events?

BackgroundInflammation is a major contributor to atherosclerotic vascular disease. Inflammatory parameters such as C-reactive protein (CRP) and Interleukin-6 (IL-6) have been shown to be strong predictors of cardiovascular events. The association between preoperative inflammatory parameters and early graft occlusion as well as cardiovascular events after coronary artery bypass grafting (CABG) has not, however, been fully elucidated. The aims of the present study were to prospectively investigate the prognostic value of the inflammatory parameters IL-6, CRP, and endothelin (ET-1) to predict early graft occlusion as well as late cardiovascular events after CABG.MethodsIn the present study 99 patients undergoing CABG because of stable angina pectoris due to significant coronary artery disease were prospectively included. Coronary angiography was repeated 3 months after CABG in 81 patients in order to evaluate early graft occlusion. Blood samples were collected before CABG in all patients. Patients were followed up for a median of 5 (3–7) years after CABG.ResultsTwenty-five patients (31%) had one or more occluded grafts at the 3-month control coronary angiography. The patients with occluded grafts had higher preoperative CRP and IL-6 levels in plasma [CRP 2.22 (1.11–4.47) mg/L vs. 1.23 (0.71–2.27) mg/L P = 0.03] and [IL-6 2.88 (1.91–5.94) pg/mL vs. 2.15 (1.54–3.14) pg/mL P = 0.006]. There were 23 late cardiovascular events among the 99 patients during the follow-up. Patients experiencing late cardiovascular events had higher preoperative IL-6 levels than those without late cardiovascular events [4.13 (1.83–5.87) pg/mL vs. 2.08 (1.53–2.29) pg/mL, P = 0.002] whereas CRP levels did not differ significantly between the two groups [1.5 (0.79–4.41) mg/L vs. 1.33 (0.74–2.48) mg/L, P = 0.41]. Looking at IL-6, a cut off value more than 3.8 pg/ml was associated with a significant higher risk for an early graft occlusion (P = 0.04) and late cardiovascular events (P = 0.00003). Preoperative endothelin-1 did not predict early graft occlusions or late cardiovascular events.ConclusionsRaised preoperative IL-6 levels are predictors of both early graft occlusion and late cardiovascular events after CABG. Elevated preoperative CRP levels can predict early graft occlusion after CABG. Endothelin did not differ between the two groups.     

Risk Stratification With the Use of Serial N-Terminal Pro–B-Type Natriuretic Peptide Measurements During Admission and Early After Discharge in Heart Failure Patients: Post Hoc Analysis of the PRIMA Study

ObjectiveThe aim of this work was to assess the prognostic value of absolute N-terminal-pro–B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge.BackgroundIn AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring.Methods and resultsWe evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13–2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76–4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13–2.89, Wald 6.1 [P = .014], respectively.ConclusionsKnowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification.     

Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) – Phase I Evaluation of the Integration and Safety of the HeartLogic Multisensor Algorithm in Patients With Heart Failure

BackgroundPatients with heart failure (HF) and reduced ejection fraction suffer from a relapsing and remitting disease course, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multisensor index and alerts in HF care.MethodsThe Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HF and reduced ejection fraction (<35%), New York Heart Association functional class II–III symptoms, implanted with a cardiac resynchronization therapy-defibrillator or and implantable cardioverter defibrillator, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (brain natriuretic peptide [BNP] of ≥150 pg/mL or N-terminal pro-BNP [NT-proBNP] of ≥600 pg/mL). This phase included the development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety.ResultsThe mean age of participants was 67 years, 68% were men, 81% were White, and 61% had a HF hospitalization in prior 12 months. During follow-up, there were 585 alert cases with an average of 1.76 alert cases per patient-year. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five serious adverse events (0.015 per patient-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (P < .001).ConclusionsHeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies.Trial RegistrationClinicalTrials.gov (NCT03237858)     

Driving Habits and Reaction Times on a Driving Simulation in Older Drivers With Chronic Heart Failure

BackgroundJudgement and reaction times during complex tasks like driving may be impaired in older adults with chronic heart failure (HF). This study sought to report the driving habits and reaction times of older patients with HF in a specially designed urban driving simulation.Methods and ResultsWe conducted a prospective observational study in HF patients and controls. Patients in both groups underwent cognitive testing and screening for depression. Current drivers undertook a questionnaire regarding driving habits followed by an urban road driving simulation consisting of 3 laps. Five separate hazards appeared in the third lap without warning. Reaction times and stopping distances to the hazards were calculated. Of 247 patients with HF approached for the study, 124 had already voluntarily stopped driving owing to HF (n = 92) or other medical conditions (n = 32), 60 had never had a license, and 32 declined to participate. Of the 74 controls approached, 1 was not currently driving owing to a medical condition and 46 declined to participate. Patients in both groups had similar levels of cognitive function, mood and driving habits. 30 patients with HF (mean age, 74 ± 5 years; median NT-proBNP 1510 pg/mL [interquartile range (IQR), 546–3084 pg/L]) and 26 controls (mean age, 73 ± 5 years; median NT-proBNP 135 pg/mL [IQR, 73–182 pg/L]) completed the simulation. During lap 3, there was no difference in the driving speed between patients (mean 22.0 ± 4.5 mph) and controls (mean 21.7 ± 3.3 mph; P = .80). Patients had longer reaction times (median, 1.10 seconds; IQR, 0.98–1.30 seconds) than controls (median, 0.96 seconds; IQR, 0.83–1.10 seconds; P = .02), but there was no difference in stopping distances (patients: median, 43.9 m [IQR, 32.2–49.5 m]; controls: median, 38.1 m [IQR, 32.3-48.8 m]; P = .31).ConclusionsMany older adults with HF no longer drive. Those who continue to drive seem to be safe to drive on simulated urban roads.     

Prognosis of Stage A or B Heart Failure Patients With Elevated B-type Natriuretic Peptide Levels

BackgroundHeart failure (HF) patients have a poor prognosis, yet outcomes might be improved by early identification of risk. We investigated the prognostic value of B-type natriuretic peptide (BNP) in patients at risk for HF (American College of Cardiology [ACC]/American Heart Association [AHA] HF Stages A and B), and compared prognosis with Stage C/D patients.Methods and ResultsOutpatients referred for echocardiogram (n = 829) were stratified by ACC/AHA HF stage and BNP levels (cutpoint of 100 pg/mL). Primary outcome was death or cardiac hospitalization at 1 year. BNP levels increased with increasing numbers of cardiovascular risk factors and with HF stage. Stage A/B patients with high BNP had a similar or worse prognosis than Stage C/D patients with low BNP. In fact, the prognosis of Stage C/D patients with low BNP did not significantly differ from the prognosis of Stage A/B patients with low BNP (adjusted HR 1.21, 95% CI 0.62–2.37), whereas Stage A/B patients with high BNP did have a significantly worse prognosis (adjusted HR 1.91, 95% CI 1.11–3.28).ConclusionsIndividuals without any history of HF but with BNP ≥100 pg/mL are at equal or higher risk than those with a HF history whose BNP is <100 pg/mL. BNP may be useful to identify asymptomatic individuals at high risk for future cardiovascular events.     

Protein Carbamylation in Chronic Systolic Heart Failure: Relationship With Renal Impairment and Adverse Long-Term Outcomes

BackgroundProtein carbamylation, a posttranslational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardiorenal function and long-term outcomes in chronic systolic heart failure (HF).Methods and ResultsIn 115 patients with chronic systolic HF (left ventricular ejection fraction ≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplantation) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 (interquartile range 59–128) μmol/mol lysine. Higher plasma PBHcit levels were associated with poorer renal function (estimated glomerular filtration rate [eGFR]: Spearman r = ?0.37; P < .001), cystatin C (r = 0.31; P = .001), and elevated plasma amino-terminal pro–B-type natriuretic peptide (NT-proBNP) levels (r = 0.26; P = .006), but not with markers of systemic inflammation or oxidant stress (high-sensitivity C-reactive protein and myeloperoxidase [MPO]: P > .10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (P > .10 for all examined) except modestly with increased right atrial volume index (r = 0.31; P = .002). PBHCit levels predicted adverse long-term events (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.3–2.6; P < .001), including after adjustment for age, eGFR, MPO, and NT-proBNP (HR 1.9, 95% CI 1.2–3.1; P = .006).ConclusionsIn chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac function, and portends poorer long-term adverse clinical outcomes even when adjusted for cardiorenal indices of adverse prognosis.     

Progression of Hyponatremia is Associated With Increased Cardiac Mortality in Patients Hospitalized for Acute Decompensated Heart Failure

BackgroundAlthough hyponatremia during hospitalization for acute decompensated heart failure (ADHF) has been reported to correlate with poor prognosis, few studies have examined the effect of progression of hyponatremia on cardiac prognosis in ADHF patients who were normonatremic at admission.Methods and ResultsConsecutive ADHF patients (n = 662) categorized as New York Heart Association Class III or IV were investigated retrospectively. Of these patients, 634 who survived to discharge were examined and 531 were normonatremic (serum sodium concentration [Na] ≥ 135 and ≤ 145 mmol/L) at admission. The 531 patients were divided into 2 groups: the non-developed group, who remained normonatremic at discharge (n = 455), and the developed group, who had progressed to hyponatremia (Na < 135 mmol/L) at discharge (n = 76). The cardiac event–free rate after 12 months was significantly lower in the developed group than in the non-developed group (22% vs. 71%; P < .0001). Although their baseline levels of brain natriuretic peptide and left ventricular ejection fraction were similar before discharge, the patients in the developed group exhibited higher fractional excretion of sodium and received higher doses of diuretics than did those in the non-developed group.ConclusionOur data suggest that progression to hyponatremia during hospitalization is a robust predictor of poor cardiac prognosis in ADHF patients who were normonatremic at admission.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

A Randomized Controlled Pilot Study of Outcomes of Strict Allowance of Fluid Therapy in Hyponatremic Heart Failure (SALT-HF)

BackgroundCurrently, fluid restriction recommendations in heart failure (HF) are based on expert opinion. After implementing a 1,000-mL/d fluid restriction for 60 days after discharge, outcomes were examined.Methods and ResultsIn a randomized controlled design, hyponatremic patients (serum sodium ≤137 mg/dL) received usual care (UC; n = 26) or 1,000 mL/d fluid restriction (n = 20) at discharge. Quality of life (QoL), thirst, difficulty following fluid recommendations, adherence to fluid restriction, HF emergency care, HF rehospitalization, and all-cause death were examined. Mean age was 62.8 ± 12.8 years; 46% were white. There were no differences by group in baseline demographics, comorbidities, and QoL, except that more UC patients had New York Heart Association (NYHA) functional class III/IV status (P = .019). Median [interquartile range] QoL scores were better in the 1,000 mL/d group for symptom burden (83.3 [68.8–91.7] vs 50 [29.2–79.2]; P = .018), total symptoms (77.1 [58.1–91.7] vs 54.2 [30.2–73.9]; P = .022), overall QoL summary (72.6 [52.2–86.3] vs 51.0 [37.7–68.5]; P = .038), and clinical QoL summary (75.5 [57.8–92.9] vs 59.1 [35.7–77.3]; P = .039). There were no group differences in thirst, difficulty adhering to fluid recommendations, adherence to fluid restriction, or health care consumption.ConclusionsThe 1,000 mL/d fluid restriction led to improved QoL at 60 days after discharge. Future research in a larger more heterogeneous sample is needed.     

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure

BackgroundIt remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression.Methods and ResultsPatients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P < .001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 m², P = .013). A multivariable Cox proportional hazard model analysis revealed that the discontinuous pattern at follow-up (P < .001) and brain natriuretic peptide (P = .021) were significantly associated with the end points, independent of age, estimated glomerular filtration rate, and serum sodium level.ConclusionsThe IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.     

Depressive Symptoms Affect the Relationship of N-Terminal Pro B-Type Natriuretic Peptide to Cardiac Event-Free Survival in Patients With Heart Failure

BackgroundBoth N-terminal pro B-type natriuretic peptide (NT-pro BNP) and depressive symptoms independently predict cardiac events in heart failure (HF) patients. However, the relationship among NT-pro BNP, depressive symptoms, and cardiac event is unknown.Methods and ResultsBlood was drawn to measure NT-pro BNP and depressive symptoms were measured by the Patient Health Questionnaire 9 (PHQ-9) among 210 patients with HF. Data about cardiac event-free survival were collected for the average follow-up period of 397 days. Cox proportional hazards regression with survival curves were used to determine the relationship of NT-pro BNP and depressive symptoms to cardiac event-free survival. Higher NT-pro-BNP confers greater risk of cardiac events among those with depressive symptoms than those without depressive symptoms (P for the interaction = .029). Patients with NT-pro BNP >581 pg/mL and total PHQ-9 score ≥10 had a 5.5 times higher risk for cardiac events compared with patients with NT-pro BNP ≤581 pg/mL and total PHQ-9 score < 10 (P = .001).ConclusionsThe prognostic association of NT-pro BNP with cardiac event-free survival in patients with HF differed by the presence of depressive symptoms. Monitoring and treatment of depressive symptoms may be important for improving cardiac event-free survival in patients with HF.     

The Impact of Heart Failure on the Classification of COPD Severity

BackgroundPulmonary restriction—a reduction of lung volumes—is common in heart failure (HF), rendering severity grading of chronic obstructive pulmonary disease (COPD) potentially problematic in subjects with both diseases. We compared pulmonary function in patients with either HF or COPD, or the combination to assess whether grading of COPD using the Global Initiative of Chronic Obstructive Lung Disease classification is hampered in the presence of HF.Methods and ResultsIn 2 cohorts involving 591 patients with established HF and 405 with a primary care diagnosis of COPD, the presence of HF and COPD was assessed according to guidelines. HF severity was staged according to the NYHA classification system into Classes I–IV. COPD was diagnosed if the ratio of post-bronchodilator forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) was <0.70, and categorized in GOLD stages I–IV according to post-bronchodilator–predicted FEV1 levels (FEV1% ≥80%; 50–79%; 30–49%; <30%). In total, 557 patients with HF only, 108 with HF+COPD, and 194 with COPD only were studied. Patients, who had neither HF nor COPD according to definition, or HF with reversible obstruction in post-bronchodilator pulmonary function tests were excluded from this analysis (n = 137). Compared with COPD only, patients with HF plus COPD had higher levels of post-bronchodilator FEV1/FVC (median [quartiles] 0.57 [0.47–0.64] vs 0.62 [0.55–0.66] and lower total lung capacity % (115 [104–126]% vs 105 [95–117]%, P < .001) P < .001), but comparable levels of post-bronchodilator FEV1% (70 [56–84]% vs 68 [54–80]%, P = .22) and thus similar distributions of GOLD stages I–IV in both groups (24/56/19/4% vs 31/50/19/1%, P = .57). In patients with HF only, 25% exhibited pre-bronchodilator FEV1% levels of <80% (FEV1% 94 [80–108]%), despite a pre-bronchodilator FEV/FVC ratio ≥0.7 in this group. The reduction of FEV1 in patients with HF only was associated with HF severity.ConclusionsIn stable HF, FEV1 may be significantly reduced even in the absence of “real” airflow obstruction. In this situation, diagnosing COPD according to GOLD criteria (based on FEV1/FVC) still seems feasible, because both FEV1 and FVC are usually decreased to an equal extent in HF. However, classifying COPD based on FEV1 levels may overrate obstruction severity in patients with combined disease (HF plus COPD), and thus may lead to unjustified use of bronchodilators.     

The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study

Purpose of Review

Biomarker-guided management of patients with chronic heart failure with reduced ejection fraction (HFrEF) remains controversial.

Recent Findings

Biomarkers have established roles for diagnosis and prognostication in HF. Pilot data suggested that use of natriuretic peptides might be helpful to guide HF care. The recent Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) randomized–controlled trial did not find therapy guided by NT-proBNP to be more effective than usual care in improving the primary endpoint of HF hospitalization or cardiovascular mortality amongst patients with chronic HFrEF. Patients in GUIDE-IT received similar care and had similar NT-proBNP lowering regardless of treatment allocation.

Summary

Though biomarkers retain important standing for diagnosis and prognosis in HF, the GUIDE-IT trial results suggest carefully managed patients may not benefit from a biomarker-guided strategy. Future studies focusing this intervention on patients treated in a more real-world setting are needed.

     

Time Course Changes in Urinary Angiotensinogen and Circulating N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized with Acute Heart Failure

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) μg/g Cr at admission; 12.1 (6.0-37.0) μg/g Cr at discharge; p<0.01] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [5,422 (2,280-9,907) pg/mL at admission; 903 (510-1,729) pg/mL at discharge; p<0.01] significantly decreased between admission and discharge along with an improvement in patient''s clinical status [New York Heart Association scores: 3 (3-4) at admission; 1 (1-1) at discharge; p<0.01]. The generalized least squares model revealed that the time course changes in uAGT/uCr also correlated with those in NT-proBNP levels between admission and readmission in five patients readmitted for HF. Conclusion The results indicated that the time course changes in uAGT/uCr correlated with those in the NT-proBNP levels in patients with HF who showed a clinical improvement. Further investigation and development of a kit for the rapid measurement of uAGT are needed to evaluate the clinical utility of uAGT as a biomarker in HF.     

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined.MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers.ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001).ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.     

Lung Ultrasound for Heart Failure Diagnosis in Primary Care

BackgroundLung ultrasound (LUS) is useful for diagnosing pulmonary congestion, but its value in primary care remains unclear. We investigated whether LUS improved diagnostic accuracy in outpatients with heart failure (HF) suspicion.Methods and resultsLUS was performed on 2 anterior (A), 2 lateral (L), and 2 posterior (P) areas per hemithorax. An area was positive when ≥3 B-lines were observed. Two diagnostic criteria were used: for LUS-C1, 2 positive areas of 4 (A-L) on each hemithorax; and for LUS-C2, 2 positive areas of 6 (A-L-P) on each hemithorax. A cardiologist blinded to LUS validated HF diagnosis. 162 patients were included (age 75.6 ± 9.4 years, 70.4% women). Both LUS criteria, alone and combined with other HF diagnostic criteria, were accurate for identifying HF. LUS-C2 outperformed LUS-C1, showing remarkable specificity (0.99) and positive predictive value (0.92). LUS-C2, together with Framingham criteria, N-terminal pro-B-type natriuretic peptide, and electrocardiogram, added diagnostic value (area under the receiver operating characteristic curves 0.90 with LUS-C2 vs 0.84 without; P = .006). In the absence of N-terminal pro-B-type natriuretic peptide, LUS-C2 significantly reclassified one-third of patients above Framingham criteria and electrocardiogram (net reclassification improvement 0.65, 95% confidence interval 0.04–1.1).ConclusionsLUS was accurate enough to rule-in HF in a primary care setting. The accuracy of diagnostic workup for HF in primary care is enhanced by incorporating LUS, irrespective NT-proBNP availability.